Biology subjects

Fujiwara, E.

Publications and source records attributed to Fujiwara, E..

3 recordsLinked to original sources

bioRxiv2026

Characterization of the Grin1Q536R/+ mouse: a preclinical model for GRIN1-related neurodevelopmental disorder

N-methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors playing critical roles in brain development, synaptic plasticity, and cognition. GRIN1-Related Neurodevelopmental Disorder (GRIN1-NDD) is a rare genetic condition caused by pathogenic variations in the GRIN1 gene, which encodes the obligatory subunit of NMDARs. The spectrum of GRIN1 clinical symptoms is hypothesized to result from the functional consequences that different missense variants have on NMDARs. To investigate the disease mechanism in vivo, we generated a novel heterozygous Grin1Q536R/+ knock-in mouse model that carries the identical variation as an adolescent male patient. We describe the clinical presentation of this patient and conduct comprehensive molecular, morphological, electrophysiological, and behavioural characterization in the juvenile, adult, and aging mice. Compared to wildtype littermates, Grin1Q536R/+ mice displayed reduced whole-cell NMDA-induced currents in cortical pyramidal neurons, and reduced NMDAR-mediated synaptic transmission, decreased long-term potentiation, but intact depotentiation at the hippocampal CA1 synapses. Morphological change was observed in the dentate gyrus region of the Grin1Q536R/+ mice. Behavioral phenotyping revealed age- and sex-dependent differences from controls, including hyperlocomotion, reduced muscle strength, and spatial learning deficits. These phenotypes are in line with the clinical manifestations and the relative disease severity of the male patient. The age-dependent phenotypic shift in Grin1Q536R/+ mice highlights the model's value for investigating GRIN1-NDD disease progression and informing longitudinal monitoring as well as potential therapeutic adjustments with age. Taken together, our findings establish a novel and robust in vivo model for studying NMDAR mechanisms and disease pathology in GRIN1-NDD, while supporting the preclinical development of new therapeutic strategies.

neuroscience↗

bioRxiv2025

Synchronous and asynchronous counterillumination by three types of photophores in the firefly squid, Watasenia scintillans

Countershading--animal body coloration that is darker on the dorsum than the ventrum--is a form of crypsis achieved through a gradient in skin pigmentation. Counterillumination is somewhat similar, achieving crypsis in midwater marine organisms by emitting downward-directed bioluminescence. Although mesopelagic squids are assumed to use counterillumination, high-resolution spatiotemporal changes in illumination, particularly for each photophore type, have not been elucidated. Watasenia scintillans has three types of photophores on its ventral surfaces: blue- and green-emitting ventral photophores and ocular photophores. It is demonstrated here that all three types of photophores are synchronously, reversibly, and repeatedly involved in counterillumination in response to changes in dim overhead lighting. Furthermore, the green-emitting photophores maintained luminescence in darkness, and their on/off switching is precisely regulated within the ambient temperature range. The photoreceptors responsible for counterillumination are extraocular photosensitive vesicles (EOPs) rather than eyes. Exposure of EOPs to visible light (blue, green, and yellow) elicited counterillumination in proportion to light intensity. No color shifts (such as from green to blue) were observed in any of the photophores. While synchronous illumination seems to support the crypsis hypothesis, the ability to independently control each photophore type could also support a previous hypothesis of conspecific signaling. Significance StatementBioluminescence is widespread among deep-sea organisms, yet the specific functions of individual light-producing organs distributed across the body surface remain underexplored. In this study, three types of ventral photophores in the firefly squid, Watasenia scintillans, were video-recorded, revealing their synchronous involvement in counterillumination--a mechanism that obscures the body silhouette when viewed from below against blue downwelling surface light. Notably, green-emitting photophores remained illuminated for extended periods in darkness, indicating a potential role in visual communication among conspecifics. The video-based techniques employed to quantify individual photophore activity provide new opportunities to investigate photo-signaling in animals inhabiting the mesopelagic zone.

animal behavior and cognition↗

bioRxiv2020

Calaxin is essential for the transmission of Ca2+-dependent asymmetric waves in sperm flagella

Regulation of waveform asymmetry in sperm flagella is critical for changes in sperm swimming trajectory as seen during sperm chemotaxis towards eggs. Ca2+ is known as an important regulator of asymmetry in flagellar waveforms. A calcium sensor protein, calaxin, which is associated with the outer arm dynein, plays a key role in the sperm waveform regulation in a Ca2+-dependent manner. However, the molecular mechanism underlying the regulation of asymmetric waves by Ca2+ and calaxin remains unclear. We performed experiments using caged ATP to elucidate the formation and propagation of asymmetric flagellar waves in the sperm of the ascidian Ciona intestinalis. Demembranated sperm cells were suspended in a solution containing caged ATP and reactivated using UV flash photolysis. Initial bends were formed at the base and propagated towards the tip of flagella; however, the bend direction was different between asymmetric and symmetric waves. A calaxin inhibitor, repaglinide, had no effect on initial bend formation, but significantly inhibited the generation of the second flagellar bend in the reverse direction, resulting in the failure of asymmetric wave formation and propagation. These results suggest that calaxin plays a critical role in Ca2+-dependent transmission of flagellar asymmetric waveforms.

cell biology↗